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Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

Medical treatment versus “Watch and Wait” in the clinical management of CE3b echinococcal cysts of the liver

Authors: Francesca Rinaldi, Annalisa De Silvestri, Francesca Tamarozzi, Federico Cattaneo, Raffaella Lissandrin, Enrico Brunetti

Published in: BMC Infectious Diseases | Issue 1/2014

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Abstract

Background

Available treatments for uncomplicated hepatic cystic echinococcosis (CE) include surgery, medical therapy with albendazole (ABZ), percutaneous interventions and the watch-and-wait (WW) approach. Current guidelines indicate that patients with hepatic CE should be assigned to each option based on cyst stage and size, and patient characteristics. However, treatment indications for transitional CE3b cysts are still uncertain. These cysts are the least responsive to non-surgical treatment and often present as indolent, asymptomatic lesions that may not warrant surgery unless complicated. Evidence supporting indications for treatment of this stage is lacking. In the attempt to fill this gap before the implementation of randomized clinical trials, we compared the clinical behavior of single hepatic CE3b cysts in 60 patients followed at the WHO Collaborating Centre for Cystic Echinococcosis of the University of Pavia.

Methods

We analyzed retrospectively data of 60 patients with hepatic CE3b cysts seen at our clinic over 27 years, who either received ABZ or were monitored with WW. Univariate and multivariate analysis were performed to investigate the effect on outcome (inactivation or relapse) of variables such as age, sex, origin, treatment, cyst size and presence of other echinococcal hepatic cysts using a multiple failure Cox proportional hazard model.

Results

ABZ treatment was positively associated with inactivation (p < 0.001), but this was not permanent, and no association was found between therapeutic approach and relapse (p = 0.091). No difference was found in the rate of complications between groups.

Conclusions

In conclusion, our study shows that ABZ treatment induces temporary inactivation of CE3b cysts, while during WW cysts remain stable over time. As the rate of adverse events during periods of ABZ treatment and WW did not differ significantly in the follow-up period considered in this study (median 43 months, IQR 10.7-141.5), expectant management might represent a valuable option for asymptomatic CE3b cysts when strict indication for surgery is absent and patients comply with regular long-term follow-up.
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Literature
1.
go back to reference Craig PS, McManus DP, Lightowlers MW, Chabalgoity JA, Garcia HH, Gavidia CM, Gilman RH, Gonzalez AE, Lorca M, Naquira C, Nieto A, Schantz PM: Prevention and control of cystic echinococcosis. Lancet Infect Dis. 2007, 7: 385-394. 10.1016/S1473-3099(07)70134-2.CrossRefPubMed Craig PS, McManus DP, Lightowlers MW, Chabalgoity JA, Garcia HH, Gavidia CM, Gilman RH, Gonzalez AE, Lorca M, Naquira C, Nieto A, Schantz PM: Prevention and control of cystic echinococcosis. Lancet Infect Dis. 2007, 7: 385-394. 10.1016/S1473-3099(07)70134-2.CrossRefPubMed
2.
go back to reference Brunetti E, White AC: Cestode infestations: hydatid disease and cysticercosis. Infect Dis Clin North Am. 2012, 26: 421-435. 10.1016/j.idc.2012.02.001.CrossRefPubMed Brunetti E, White AC: Cestode infestations: hydatid disease and cysticercosis. Infect Dis Clin North Am. 2012, 26: 421-435. 10.1016/j.idc.2012.02.001.CrossRefPubMed
3.
go back to reference McManus DP, Zhang W, Li J, Bartley PB: Echinococcosis. Lancet. 2003, 362: 1295-1304. 10.1016/S0140-6736(03)14573-4.CrossRefPubMed McManus DP, Zhang W, Li J, Bartley PB: Echinococcosis. Lancet. 2003, 362: 1295-1304. 10.1016/S0140-6736(03)14573-4.CrossRefPubMed
4.
go back to reference Brunetti E, Kern P, Vuitton DA: Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta Trop. 2010, 114: 1-16. 10.1016/j.actatropica.2009.11.001.CrossRefPubMed Brunetti E, Kern P, Vuitton DA: Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta Trop. 2010, 114: 1-16. 10.1016/j.actatropica.2009.11.001.CrossRefPubMed
5.
go back to reference Stojkovic M, Rosenberger K, Kauczor HU, Junghanss T, Hosch W: Diagnosing and staging of cystic echinococcosis: how do CT and MRI perform in comparison to ultrasound?. PLoS Negl Trop Dis. 2012, 6: e1880-10.1371/journal.pntd.0001880.CrossRefPubMedPubMedCentral Stojkovic M, Rosenberger K, Kauczor HU, Junghanss T, Hosch W: Diagnosing and staging of cystic echinococcosis: how do CT and MRI perform in comparison to ultrasound?. PLoS Negl Trop Dis. 2012, 6: e1880-10.1371/journal.pntd.0001880.CrossRefPubMedPubMedCentral
6.
go back to reference WHO-IWGE: International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop. 2003, 85: 253-261. 10.1016/S0001-706X(02)00223-1.CrossRef WHO-IWGE: International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop. 2003, 85: 253-261. 10.1016/S0001-706X(02)00223-1.CrossRef
7.
go back to reference Hosch W, Junghanss T, Stojkovic M, Brunetti E, Heye T, Kauffmann GW, Hull WE: Metabolic viability assessment of cystic echinococcosis using high-field 1H MRS of cyst contents. NMR Biomed. 2008, 21: 734-754. 10.1002/nbm.1252.CrossRefPubMed Hosch W, Junghanss T, Stojkovic M, Brunetti E, Heye T, Kauffmann GW, Hull WE: Metabolic viability assessment of cystic echinococcosis using high-field 1H MRS of cyst contents. NMR Biomed. 2008, 21: 734-754. 10.1002/nbm.1252.CrossRefPubMed
8.
go back to reference Golemanov B, Grigorov N, Mitova R, Genov J, Vuchev D, Tamarozzi F, Brunetti E: Efficacy and safety of PAIR for cystic echinococcosis: experience on a large series of patients from Bulgaria. Am J Trop Med Hyg. 2011, 84: 48-51. 10.4269/ajtmh.2011.10-0312.CrossRefPubMedPubMedCentral Golemanov B, Grigorov N, Mitova R, Genov J, Vuchev D, Tamarozzi F, Brunetti E: Efficacy and safety of PAIR for cystic echinococcosis: experience on a large series of patients from Bulgaria. Am J Trop Med Hyg. 2011, 84: 48-51. 10.4269/ajtmh.2011.10-0312.CrossRefPubMedPubMedCentral
9.
go back to reference Gharbi HA, Hassine W, Brauner MW, Dupuch K: Ultrasound examination of the hydatic liver. Radiology. 1981, 139: 459-463. 10.1148/radiology.139.2.7220891.CrossRefPubMed Gharbi HA, Hassine W, Brauner MW, Dupuch K: Ultrasound examination of the hydatic liver. Radiology. 1981, 139: 459-463. 10.1148/radiology.139.2.7220891.CrossRefPubMed
10.
go back to reference Brunetti EGH, Junghanss T: on behalf of the members of the International CE Workshop in Lima, Peru,2009: Cystic echinococcosis: chronic, complex, and still neglected. PLoS Negl Trop Dis. 2011, 5: e1146-10.1371/journal.pntd.0001146.CrossRefPubMedPubMedCentral Brunetti EGH, Junghanss T: on behalf of the members of the International CE Workshop in Lima, Peru,2009: Cystic echinococcosis: chronic, complex, and still neglected. PLoS Negl Trop Dis. 2011, 5: e1146-10.1371/journal.pntd.0001146.CrossRefPubMedPubMedCentral
11.
go back to reference Kabaalioglu A, Ceken K, Alimoglu E, Apaydin A: Percutaneous imaging-guided treatment of hydatid liver cysts: do long-term results make it a first choice?. Eur J Radiol. 2006, 59: 65-73. 10.1016/j.ejrad.2006.01.014.CrossRefPubMed Kabaalioglu A, Ceken K, Alimoglu E, Apaydin A: Percutaneous imaging-guided treatment of hydatid liver cysts: do long-term results make it a first choice?. Eur J Radiol. 2006, 59: 65-73. 10.1016/j.ejrad.2006.01.014.CrossRefPubMed
12.
go back to reference WHO-IWGE: Puncture, aspiration, injection, re-aspiration. An option for the treatment of cystic echinococcosis. Book Puncture, aspiration, injection, re-aspiration. An option for the treatment of cystic echinococcosis. (Editor ed.^eds.), vol. Document WHO/CDS/CSR/APH/2001.6. 2001, City: World Health Organization, 1-40. WHO-IWGE: Puncture, aspiration, injection, re-aspiration. An option for the treatment of cystic echinococcosis. Book Puncture, aspiration, injection, re-aspiration. An option for the treatment of cystic echinococcosis. (Editor ed.^eds.), vol. Document WHO/CDS/CSR/APH/2001.6. 2001, City: World Health Organization, 1-40.
13.
go back to reference Junghanss T, da Silva AM, Horton J, Chiodini PL, Brunetti E: Clinical management of cystic echinococcosis: state of the art, problems, and perspectives. Am J Trop Med Hyg. 2008, 79: 301-311.PubMed Junghanss T, da Silva AM, Horton J, Chiodini PL, Brunetti E: Clinical management of cystic echinococcosis: state of the art, problems, and perspectives. Am J Trop Med Hyg. 2008, 79: 301-311.PubMed
14.
go back to reference Horton RJ: Albendazole in treatment of human cystic echinococcosis: 12 years of experience. Acta Trop. 1997, 64: 79-93. 10.1016/S0001-706X(96)00640-7.CrossRefPubMed Horton RJ: Albendazole in treatment of human cystic echinococcosis: 12 years of experience. Acta Trop. 1997, 64: 79-93. 10.1016/S0001-706X(96)00640-7.CrossRefPubMed
15.
go back to reference Teggi A, Lastilla MG, De Rosa F: Therapy of human hydatid disease with mebendazole and albendazole. Antimicrob Agents Chemother. 1993, 37: 1679-1684. 10.1128/AAC.37.8.1679.CrossRefPubMedPubMedCentral Teggi A, Lastilla MG, De Rosa F: Therapy of human hydatid disease with mebendazole and albendazole. Antimicrob Agents Chemother. 1993, 37: 1679-1684. 10.1128/AAC.37.8.1679.CrossRefPubMedPubMedCentral
16.
go back to reference Piccoli L, Meroni V, Genco F, Tamarozzi F, Tinelli C, Filice C, Brunetti E: Serum cytokine profile by ELISA in patients with echinococcal cysts of the liver: a stage-specific approach to assess their biological activity. Clin Dev Immunol. 2012, 2012: 483935-CrossRefPubMedPubMedCentral Piccoli L, Meroni V, Genco F, Tamarozzi F, Tinelli C, Filice C, Brunetti E: Serum cytokine profile by ELISA in patients with echinococcal cysts of the liver: a stage-specific approach to assess their biological activity. Clin Dev Immunol. 2012, 2012: 483935-CrossRefPubMedPubMedCentral
17.
go back to reference Moro PL, Gilman RH, Verastegui M, Bern C, Silva B, Bonilla JJ: Human hydatidosis in the central Andes of Peru: evolution of the disease over 3 years. Clin Infect Dis. 1999, 29: 807-812. 10.1086/520440.CrossRefPubMed Moro PL, Gilman RH, Verastegui M, Bern C, Silva B, Bonilla JJ: Human hydatidosis in the central Andes of Peru: evolution of the disease over 3 years. Clin Infect Dis. 1999, 29: 807-812. 10.1086/520440.CrossRefPubMed
18.
go back to reference Frider B, Larrieu E, Odriozola M: Long-term outcome of asymptomatic liver hydatidosis. J Hepatol. 1999, 30: 228-231. 10.1016/S0168-8278(99)80066-X.CrossRefPubMed Frider B, Larrieu E, Odriozola M: Long-term outcome of asymptomatic liver hydatidosis. J Hepatol. 1999, 30: 228-231. 10.1016/S0168-8278(99)80066-X.CrossRefPubMed
19.
go back to reference Franchi C, Di Vico B, Teggi A: Long-term evaluation of patients with hydatidosis treated with benzimidazole carbamates. Clin Infect Dis. 1999, 29: 304-309. 10.1086/520205.CrossRefPubMed Franchi C, Di Vico B, Teggi A: Long-term evaluation of patients with hydatidosis treated with benzimidazole carbamates. Clin Infect Dis. 1999, 29: 304-309. 10.1086/520205.CrossRefPubMed
20.
go back to reference Paksoy Y, Odev K, Sahin M, Arslan A, Koc O: Percutaneous treatment of liver hydatid cysts: comparison of direct injection of albendazole and hypertonic saline solution. AJR Am J Roentgenol. 2005, 185: 727-734. 10.2214/ajr.185.3.01850727.CrossRefPubMed Paksoy Y, Odev K, Sahin M, Arslan A, Koc O: Percutaneous treatment of liver hydatid cysts: comparison of direct injection of albendazole and hypertonic saline solution. AJR Am J Roentgenol. 2005, 185: 727-734. 10.2214/ajr.185.3.01850727.CrossRefPubMed
21.
go back to reference Nahmias J, Goldsmith R: Soibelman M, el-On J: Three- to 7-year follow-up after albendazole treatment of 68 patients with cystic echinococcosis (hydatid disease). Ann Trop Med Parasitol. 1994, 88: 295-304.PubMed Nahmias J, Goldsmith R: Soibelman M, el-On J: Three- to 7-year follow-up after albendazole treatment of 68 patients with cystic echinococcosis (hydatid disease). Ann Trop Med Parasitol. 1994, 88: 295-304.PubMed
22.
go back to reference Morris DL, Smith PG: Albendazole in hydatid disease–hepatocellular toxicity. Trans R Soc Trop Med Hyg. 1987, 81: 343-344. 10.1016/0035-9203(87)90259-8.CrossRefPubMed Morris DL, Smith PG: Albendazole in hydatid disease–hepatocellular toxicity. Trans R Soc Trop Med Hyg. 1987, 81: 343-344. 10.1016/0035-9203(87)90259-8.CrossRefPubMed
23.
go back to reference Gil-Grande LA, Rodriguez-Caabeiro F, Prieto JG, Sanchez-Ruano JJ, Brasa C, Aguilar L, Garcia-Hoz F, Casado N, Barcena R, Alvarez AI, Dal-RéR : Randomised controlled trial of efficacy of albendazole in intra-abdominal hydatid disease. Lancet. 1993, 342: 1269-1272. 10.1016/0140-6736(93)92361-V.CrossRefPubMed Gil-Grande LA, Rodriguez-Caabeiro F, Prieto JG, Sanchez-Ruano JJ, Brasa C, Aguilar L, Garcia-Hoz F, Casado N, Barcena R, Alvarez AI, Dal-RéR : Randomised controlled trial of efficacy of albendazole in intra-abdominal hydatid disease. Lancet. 1993, 342: 1269-1272. 10.1016/0140-6736(93)92361-V.CrossRefPubMed
24.
go back to reference Opatrny L, Prichard R, Snell L, Maclean JD: Death related to albendazole-induced pancytopenia: case report and review. Am J Trop Med Hyg. 2005, 72: 291-294.PubMed Opatrny L, Prichard R, Snell L, Maclean JD: Death related to albendazole-induced pancytopenia: case report and review. Am J Trop Med Hyg. 2005, 72: 291-294.PubMed
25.
go back to reference Brunetti E, Filice C: Radiofrequency thermal ablation of echinococcal liver cysts. Lancet. 2001, 358: 1464-CrossRefPubMed Brunetti E, Filice C: Radiofrequency thermal ablation of echinococcal liver cysts. Lancet. 2001, 358: 1464-CrossRefPubMed
26.
go back to reference Piccoli L, Bazzocchi C, Brunetti E, Mihailescu P, Bandi C, Mastalier B, Cordos I, Beuran M, Popa LG, Meroni V, Genco F, Cretu C: Molecular characterization of Echinococcusgranulosus in south-eastern Romania: evidence of G1-G3 and G6-G10 complexes in humans. Clin Microbiol Infect. 2013, 19: 578-582. 10.1111/j.1469-0691.2012.03993.x.CrossRefPubMed Piccoli L, Bazzocchi C, Brunetti E, Mihailescu P, Bandi C, Mastalier B, Cordos I, Beuran M, Popa LG, Meroni V, Genco F, Cretu C: Molecular characterization of Echinococcusgranulosus in south-eastern Romania: evidence of G1-G3 and G6-G10 complexes in humans. Clin Microbiol Infect. 2013, 19: 578-582. 10.1111/j.1469-0691.2012.03993.x.CrossRefPubMed
27.
go back to reference Sharma M, Sehgal R, Fomda BA, Malhotra A, Malla N: Molecular characterization of Echinococcus granulosus cysts in north Indian patients: identification of G1, G3, G5 and G6 genotypes. PLoS Negl Trop Dis. 2013, 7: e2262-10.1371/journal.pntd.0002262.CrossRefPubMedPubMedCentral Sharma M, Sehgal R, Fomda BA, Malhotra A, Malla N: Molecular characterization of Echinococcus granulosus cysts in north Indian patients: identification of G1, G3, G5 and G6 genotypes. PLoS Negl Trop Dis. 2013, 7: e2262-10.1371/journal.pntd.0002262.CrossRefPubMedPubMedCentral
28.
go back to reference Mogoye BK, Menezes CN, Wong ML, Stacey S, von Delft D, Wahlers K, Wassermann M, Romig T, Kern P, Grobusch MP, Frean J: First insights into species and genotypes of Echinococcus in South Africa. Vet Parasitol. 2013, 196: 427-432. 10.1016/j.vetpar.2013.03.033.CrossRefPubMed Mogoye BK, Menezes CN, Wong ML, Stacey S, von Delft D, Wahlers K, Wassermann M, Romig T, Kern P, Grobusch MP, Frean J: First insights into species and genotypes of Echinococcus in South Africa. Vet Parasitol. 2013, 196: 427-432. 10.1016/j.vetpar.2013.03.033.CrossRefPubMed
29.
go back to reference Liu Q, Cao L, Zhang Y, Xu D, Shang L, Wang X, Wei F, Xiao L, Ma R, Cai J, Zhao Q: Genotypes of Echinococcus granulosus in animals from Yushu, Northeastern China. Vector Borne Zoonotic Dis. 2013, 13: 134-137. 10.1089/vbz.2012.1050.CrossRefPubMed Liu Q, Cao L, Zhang Y, Xu D, Shang L, Wang X, Wei F, Xiao L, Ma R, Cai J, Zhao Q: Genotypes of Echinococcus granulosus in animals from Yushu, Northeastern China. Vector Borne Zoonotic Dis. 2013, 13: 134-137. 10.1089/vbz.2012.1050.CrossRefPubMed
30.
go back to reference Abushhewa MH, Abushhiwa MH, Nolan MJ, Jex AR, Campbell BE, Jabbar A, Gasser RB: Genetic classification of Echinococcus granulosus cysts from humans, cattle and camels in Libya using mutation scanning-based analysis of mitochondrial loci. Mol Cell Probes. 2010, 24: 346-351. 10.1016/j.mcp.2010.07.005.CrossRefPubMed Abushhewa MH, Abushhiwa MH, Nolan MJ, Jex AR, Campbell BE, Jabbar A, Gasser RB: Genetic classification of Echinococcus granulosus cysts from humans, cattle and camels in Libya using mutation scanning-based analysis of mitochondrial loci. Mol Cell Probes. 2010, 24: 346-351. 10.1016/j.mcp.2010.07.005.CrossRefPubMed
31.
go back to reference Boubaker G, Macchiaroli N, Prada L, Cucher MA, Rosenzvit MC, Ziadinov I, Deplazes P, Saarma U, Babba H, Gottstein B, Spiliotis M: A multiplex PCR for the simultaneous detection and genotyping of the Echinococcus granulosus complex. PLoS Negl Trop Dis. 2013, 7: e2017-10.1371/journal.pntd.0002017.CrossRefPubMedPubMedCentral Boubaker G, Macchiaroli N, Prada L, Cucher MA, Rosenzvit MC, Ziadinov I, Deplazes P, Saarma U, Babba H, Gottstein B, Spiliotis M: A multiplex PCR for the simultaneous detection and genotyping of the Echinococcus granulosus complex. PLoS Negl Trop Dis. 2013, 7: e2017-10.1371/journal.pntd.0002017.CrossRefPubMedPubMedCentral
32.
go back to reference Stojkovic M, Zwahlen M, Teggi A, Vutova K, Cretu CM, Virdone R, Nicolaidou P, Cobanoglu N, Junghanss T: Treatment response of cystic echinococcosis to benzimidazoles: a systematic review. PLoS Negl Trop Dis. 2009, 3: e524-10.1371/journal.pntd.0000524.CrossRefPubMedPubMedCentral Stojkovic M, Zwahlen M, Teggi A, Vutova K, Cretu CM, Virdone R, Nicolaidou P, Cobanoglu N, Junghanss T: Treatment response of cystic echinococcosis to benzimidazoles: a systematic review. PLoS Negl Trop Dis. 2009, 3: e524-10.1371/journal.pntd.0000524.CrossRefPubMedPubMedCentral
33.
go back to reference Neumayr A, Troia G, de Bernardis C, Tamarozzi F, Goblirsch S, Piccoli L, Hatz C, Filice C, Brunetti E: Justified concern or exaggerated fear: the risk of anaphylaxis in percutaneous treatment of cystic echinococcosis-a systematic literature review. PLoS Negl Trop Dis. 2011, 5: e1154-10.1371/journal.pntd.0001154.CrossRefPubMedPubMedCentral Neumayr A, Troia G, de Bernardis C, Tamarozzi F, Goblirsch S, Piccoli L, Hatz C, Filice C, Brunetti E: Justified concern or exaggerated fear: the risk of anaphylaxis in percutaneous treatment of cystic echinococcosis-a systematic literature review. PLoS Negl Trop Dis. 2011, 5: e1154-10.1371/journal.pntd.0001154.CrossRefPubMedPubMedCentral
Metadata
Title
Medical treatment versus “Watch and Wait” in the clinical management of CE3b echinococcal cysts of the liver
Authors
Francesca Rinaldi
Annalisa De Silvestri
Francesca Tamarozzi
Federico Cattaneo
Raffaella Lissandrin
Enrico Brunetti
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-492

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